Duplicated hepatic artery: radiologic and surgical implications.
Preoperative angiography of the coeliac trunk and superior mesenteric artery is routinely performed before liver resections and transplantations. For this purpose, it is usual to inject each branch of the coeliac trunk separately. Selective angiographic studies, however, may lead to overlooking surgically essential anatomic variations of the hepatic blood supply, as demonstrated by the present report. A case of a duplicated hepatic artery is presented, its radiologic and surgical implications discussed, and the relevant literature reviewed. This uncommon and particularly evocative feature illustrates the clinical importance of a sound knowledge of anatomical variants.


Dosimetric Uncertainties Resulting From Interfractional Anatomic Variations for Patients Receiving Pancreas Stereotactic Body Radiation Therapy and Cone Beam Computed Tomography Image Guidance.
To estimate the effects of interfractional anatomic changes on dose to organs at risk (OARs) and tumors, as measured with cone beam computed tomography (CBCT) image guidance for pancreatic stereotactic body radiation therapy. We evaluated 11 patients with pancreatic cancer whom were treated with stereotactic body radiation therapy (33-40 Gy in 5 fractions) using daily CT-on-rails (CTOR) image guidance immediately before treatment with breath-hold motion management. CBCT alignment was simulated in the treatment planning software by aligning the original planning CT to each fractional CTOR image set via fiducial markers. CTOR data sets were used to calculate fractional doses after alignment by applying the rigid shift of the planning CT and CTOR image sets to the planning treatment isocenter and recalculating the fractional dose. Accumulated dose to the gross tumor volume (GTV), tumor vessel interface, duodenum, small bowel, and stomach were calculated by summing the 5 fractional absolute dose-volume histograms into a single dose-volume histogram for comparison with the original planned dose. Four patients had a GTV D100% of at least 1.5 Gy less than the fractional planned value in several fractions; 4 patients had fractional underestimation of duodenum dose by 1.0 Gy per fraction. The D1.0 cm3 <35 Gy constraint was violated for at least 1 OAR in 3 patients, with either the duodenum (n = 2) or small bowel (n = 1) D1.0 cm3 being higher on the accumulated dose distribution (P = .01). D100% was significantly lower according to accumulated dose GTV (P = .01) and tumor vessel interface (P = .02), with 4 and 2 patients having accumulated D100% ≥4 Gy lower than the planned value for the GTV and tumor vessel interface, respectively. For some patients, CBCT image guidance based on fiducial alignment may cause large dosimetric uncertainties for OARs and target structures, according to accumulated dose.


Integration of universal design of instruction in occupational therapy professional education: responding to student diversity.
Application of the seven principles of universal design of instruction in occupational therapy education is intended to meet the diverse learning needs of students and provide full access to educational experiences without disadvantaging some students (Bowe, 2000; Burgstahler, 2001; McGuire & Scott, 2002). The intended outcome is success for all students. Further, universal design of instruction is congruent with the occupational therapy core value of mutual respect, whereby... We treat people fairly and equitably. We acknowledge and support others regardless of differences. We appreciate their qualities, capabilities and contributions (American Occupational Therapy Association, 2003). While the benefits of universal design of instruction in occupational therapy curricula appear to be extensive, a caveat must be included. Use of any instructional design tool is legitimized when grounded in research. Though literature in multiple disciplines is expanding related to universal design of instruction, we need research specific to occupational therapy education.


Preliminary report on radiation and heart disease.
Using data from the Tri-State and a mathematical model, the hypothesis that low levels of diagnostic radiation can produce both leukemia and heart disease has been tested. The range of radiation considered is within a factor of 10 of 5 rads (0.5-50 rads). Even at the lowest levels, an estimated 5% of the persons exposed suffer damage to the DNA which is subsequently expressed as heart disease or leukemia. The risk of heart disease in an affected group is roughly tripled and there is a 10-fold increase in the risk of leukemia according to preliminary estimates.


Quantitative 19F MRI of perfluoro-15-crown-5-ether using uniformity correction of the spin excitation and signal reception.
A common limitation of all 1H contrast agents is that they only allow indirect visualization through modification of the intrinsic properties of the tissue, making quantification of this effect challenging. 19F compounds, on the contrary, are measured directly, without any background signal. There is a linear relationship between the amount of 19F spins and the intensity of the signal. However, non-uniformity of the radiofrequency field may lead to errors in the quantified 19F signal and should be carefully addressed for any quantitative imaging. Adaptation of the previously introduced [Formula: see text] mapping technique to the problem of quantifying the 19F signal from perfluoro-15-crown-5-ether (PFCE) is proposed in this work. Initial evaluation of the proposed technique simultaneously accounting for transmit [Formula: see text] and receive [Formula: see text] field inhomogeneities is performed in a PFCE phantom. As a proof of concept, in vivo quantification of the 19F signal is performed in a murine model after application of custom-designed hollow mesoporous silica spheres (HMSS) loaded with PFCE. A phantom experiment clearly shows that only compensation for both transmit and receive characteristics outperforms inaccurate quantification based on the non- or partly-corrected signal intensities. Furthermore, an optimized protocol is proposed for in vivo application. The proposed [Formula: see text]/[Formula: see text] mapping technique represents a simple to implement and easy-to-use solution for quantification of the 19F signal from PFCE in the presence of B1-field inhomogeneities.


Efficacy of Psychosocial and Psychological Interventions in Addition to Drug Therapy to Improve Global Functioning of Inpatients with Schizophrenia Spectrum and Mood Disorders: A Real-World Observational Study.
Psychotic and mood disorders are associated with significant functional impairment, premature mortality, physical morbidity, and great social and economic burden. The aim of this study is to evaluate the effectiveness of psychosocial, psychological, and rehabilitative interventions implemented in an Italian psychiatric inpatient facility, with a focus on patients with schizophrenia spectrum versus those with mood disorders. A retrospective observational study was conducted in the psychiatric hospital Villa Maria Pia in Rome, Italy, during 2022. Patients with an established diagnosis of schizophrenia spectrum and mood disorder (ICD-9-CM) were assessed on admission (T0) and at the end of treatment (T1), using the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF). Interventions involved a multidisciplinary team and included individual and group activities. The t-test for independent samples was used to compare continuous variables between groups and Spearman correlation coefficient to calculate correlations between variables. The study sample consisted of 141 patients, the majority of them being adults (51.3 years ± 12.4) men (F/M= 68/73). Among them, 85 patients (60.3%) actively engaged in psychosocial and rehabilitative interventions and, compared to non-participating individuals, they showed lower functioning and symptoms at discharge (delta GAF was significantly higher among patients who had taken part in the psychosocial activities, t = -2.095; p = 0.038). Considering the index computed (n of interventions/days of hospitalization), the number of psychosocial activities was positively correlated with the improvement in patients' functioning in the sample taking part in activities (r = 0.272, p = 0.012), especially with psychotherapy and support groups (r = 0.202, p = 0.017 and r = 0.188, p = 0.025, respectively). Splitting the total sample into schizophrenia-spectrum disorder (N = 37) and mood disorder (N = 48) groups, the positive correlations between GAF improvement and participation in psychosocial activities were confirmed only in the schizophrenia-spectrum group. These correlations were not significant for symptomatology (BPRS) either in the total or the individual group. Evidence from our study suggests that inpatient rehabilitation can be effective and useful for people with severe mental disorders. Further investigations are needed to better understand its effectiveness on improving quality of life and social functioning in the long term.


Combined iridium 192 interstitial and external beam radiation therapy for the treatment of prostatic cancer.
Twenty-four patients with clinically palpable prostatic adenocarcinoma (stage B or C) were treated with a combination of interstitial radiation therapy and external beam radiation therapy following pelvic lymphadenectomy for accurate staging. Early results indicate a complete clinical response rate at 12 months of 77%, with a 4% complication rate (persisting rectal ulceration).


An infrared spectroscopy study of acid stability and thermal unfolding process of granulocyte-colony stimulating factor.
Temperature-dependent (25-80 degrees C) infrared (IR) spectra were obtained for recombinant methionyl human granulocyte-colony stimulating factor (rmethuG-CSF) in aqueous solutions over the pD range of 5.5-2.1 to investigate its thermal stability at various pDs. Second derivative, Fourier self-deconvolution, and curve-fitting analyses were performed to analyze the obtained spectra. These spectral analyses demonstrated that in the thermal unfolding process the alpha-helix structure of rmethuG-CSF partially changes to an unordered structure and then the unordered structure forms aggregates. The temperature-dependent IR spectra revealed that the structure of rmethuG-CSF is the most stable at pD 2.5 in the pD range of 5.5-2.1. It has been suggested that the unordered structure formed before the marked structural change in the whole molecule is a perturbed form of the native structure of rmethuG-CSF and plays a role as a precursor for the aggregation. This alteration to the perturbed form is likely to be the first secondary structure change that occurs along the aggregation pathway. Of particular note is that the stability at pD 2.1 is slightly lower than that at pD 2.5, but that aggregates are formed at higher temperature at pD 2.1 than at pD 2.5, probably because the repulsive interaction between the unordered structure is stronger at pD 2.1.


Psychometric properties of the Posttraumatic Avoidance Behaviour Questionnaire among a treatment-seeking adult sample.
Avoidance of trauma-related stimuli is thought to be central in the development and maintenance of posttraumatic stress disorder (PTSD). However, knowledge of trauma-related avoidance has been limited by conceptualization of this construct as unifactorial and consisting of only two components. The Posttraumatic Avoidance Behaviour Questionnaire (PABQ; van Minnen & Hagenaars, 2010) was developed to assess distinct domains of avoidance. The current study expanded upon one prior psychometric study of the PABQ by examining the internal consistency and construct validity of the PABQ among a sample of 177 treatment-seeking adults diagnosed with PTSD. Results indicated that the psychometric properties vary by PABQ subscale. Although all subscales demonstrated adequate internal consistency, items that appear to be negatively impacting internal consistency were identified for several subscales. Although correlations between PABQ subscales indicate subscales index distinct dimensions of trauma-related avoidance, observed similar associations with external correlates suggest these subscales may not functionally differ in their association with PTSD symptoms and co-occurring psychopathology. Accordingly, results suggest further construct validity evidence is needed to determine whether, despite potentially representing distinct domains of avoidance, avoidance of different forms of trauma-related stimuli predicts functionally distinct outcomes. Collectively, our results indicate that the PABQ is a potentially promising measure for assessing trauma-related avoidance behavior, although additional research is needed to better understand the degree to which these hypothesized distinct domains of avoidance behaviors represent meaningfully distinct constructs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Elimination of oral food challenge reaction by injection of food extracts. A double-blind evaluation.
Twenty subjects underwent a double-blind evaluation by analyzing six variables to determine if subcutaneous injection of the food extract neutralizing dose would protect subjects from reactions. Twelve subjects had four of the six variables neutralized 60% of the time following the food antigen neutralizing dose. The placebo trials neutralized four of six variables 15% of the time. The sign/symptom results show statistical significance favoring food extract neutralization over placebo. The remaining eight subjects had at least two of the six variables neutralized by the food extract up to 85% of the time. It appears that the phenomenon of subcutaneous food neutralization can be scientifically endorsed for clinical use in the treatment of food reactions.


Automated image quality evaluation of T2 -weighted liver MRI utilizing deep learning architecture.
To develop and test a deep learning approach named Convolutional Neural Network (CNN) for automated screening of T2 -weighted (T2 WI) liver acquisitions for nondiagnostic images, and compare this automated approach to evaluation by two radiologists. We evaluated 522 liver magnetic resonance imaging (MRI) exams performed at 1.5T and 3T at our institution between November 2014 and May 2016 for CNN training and validation. The CNN consisted of an input layer, convolutional layer, fully connected layer, and output layer. 351 T2 WI were anonymized for training. Each case was annotated with a label of being diagnostic or nondiagnostic for detecting lesions and assessing liver morphology. Another independently collected 171 cases were sequestered for a blind test. These 171 T2 WI were assessed independently by two radiologists and annotated as being diagnostic or nondiagnostic. These 171 T2 WI were presented to the CNN algorithm and image quality (IQ) output of the algorithm was compared to that of two radiologists. There was concordance in IQ label between Reader 1 and CNN in 79% of cases and between Reader 2 and CNN in 73%. The sensitivity and the specificity of the CNN algorithm in identifying nondiagnostic IQ was 67% and 81% with respect to Reader 1 and 47% and 80% with respect to Reader 2. The negative predictive value of the algorithm for identifying nondiagnostic IQ was 94% and 86% (relative to Readers 1 and 2). We demonstrate a CNN algorithm that yields a high negative predictive value when screening for nondiagnostic T2 WI of the liver. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:723-728.


YfaE, a ferredoxin involved in diferric-tyrosyl radical maintenance in Escherichia coli ribonucleotide reductase.
Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides in all organisms. The class I RNRs are composed of a 1:1 complex of two homodimeric subunits: alpha and beta. beta contains the diferric-tyrosyl radical (Y*) cofactor essential for the reduction process. In vivo, the mechanism of Y* regeneration from the diferric-beta2 (met-beta2) or apo-beta2 is still unclear. Y* regenerations from met-beta2 and apo-beta2 have been designated the maintenance and biosynthetic pathways, respectively. To understand these two pathways, 181 genomes that contain nrdAnrdB (genes encoding alpha and beta) were examined. In 29% of the cases, an open reading frame annotated 2Fe2S ferredoxin (YfaE in Escherichia coli) is located next to nrdB. Thus, YfaE has been cloned, expressed, resolubilized, reconstituted anaerobically with Fe2+, Fe3+, and S2-, and characterized by Mössbauer, EPR, and visible spectroscopies. Titration of met-beta2 with [2Fe2S]1+-YfaE anaerobically results in the formation of an equilibrium mixture of diferrous-beta2 and [2Fe2S]2+-YfaE with one Fe reduced/YfaE oxidized. At the end point of the titration, O2 is added to the mixture and the diferrous-beta2 rapidly undergoes reaction to form the diferric-Y* with a stoichiometry of 2Fe/Y* and a specific activity correlated to the amount of Y*. The reducing equivalent required for diferric-Y* cofactor biosynthesis is supplied by beta. Under anaerobic conditions, stopped flow kinetics have been used to monitor the disappearance of the diferric cluster and the formation of [2Fe2S]2+-YfaE. The titrations and kinetic studies provide the first evidence for a protein involved in the maintenance pathway and likely the biosynthetic pathway.


A comparative population-based study of prostate cancer incidence and mortality rates in Singapore, Sweden and Geneva, Switzerland from 1973 to 2006.
Prostate cancer is the most commonly diagnosed malignancy in men in Sweden and Geneva, and the third most common in men in Singapore. This population-based study describes trends in the incidence and mortality rates of prostate cancer in Singapore, Sweden and Geneva (Switzerland) from 1973 to 2006 and explores possible explanations for these different trends. Data from patients diagnosed with prostate cancer were extracted from national cancer registries in Singapore (n = 5,172), Sweden (n = 188,783) and Geneva (n = 5,755) from 1973 to 2006. Trends of incidence and mortality were reported using the Poisson and negative binomial regression models. The age, period and birth-cohort were tested as predictors of incidence and mortality rates of prostate cancer. Incidence rates of prostate cancer increased over all time periods for all three populations. Based on the age-period-cohort analysis, older age and later period of diagnosis were associated with a higher incidence of prostate cancer, whereas older age and earlier period were associated with higher mortality rates for prostate cancer in all three countries. This study demonstrated an overall increase in incidence rates and decrease in mortality rates in Singapore, Sweden and Geneva. Both incidence and mortality rates were much lower in Singapore. The period effect is a stronger predictor of incidence and mortality of prostate cancer than the birth-cohort effect.


Serial mechanisms in lexical access: the rank hypothesis.
There is general agreement that the effect of frequency on lexical access time is roughly logarithmic, although little attention has been given to the reason for this. The authors argue that models of lexical access that incorporate a frequency-ordered serial comparison or verification procedure provide an account of this effect and predict that the underlying function directly relates access time to the rank order of words in a frequency-ordered set. For both group data and individual data, it is shown that rank provides a better fit to the data than does a function based on log frequency. Extensions to a search model are proposed that account for error rates and latencies and the effect of age of acquisition, which is interpreted as an effect of cumulative frequency.


Hip fractures--patient background.
A consecutive series of 282 patients with hip fractures, with a mean age of 76 years, was studied. Two-thirds of the patients (182) lived in their own homes, half of them alone and one-third of the 182 requiring regular help. Widows were more common in the age group 75-84 years and widowers and single men in the age group 65-74 years. Thirty % of the patients used walking aids and had previously sustained fractures of the osteoporotic type. One-fourth of the patients were confused on arrival at hospital. Laboratory tests differed little from values in the normal population. Chest X-ray was of value and cardiac decompensation was diagnosed in a small group. Time aspects of the hip fracture accident are discussed. No increase in incidence in the age group over 70 years was found during the period 1971-1981.


The evaluation of nailfold videocapillaroscopy findings in patients with type 2 diabetes with and without diabetic retinopathy.
Diabetes mellitus (DM) is a chronic hyperglycemic state and is associated with microvascular structural alterations. This study aimed to investigate the diameters of capillary loops and morphostructural changes using nailfold video capillaroscopy (NVC) in patients with type 2 DM with and without diabetic retinopathy (DR). This cross-sectional, single-center study was conducted in patients with type 2 DM who were followed in outpatient clinics of ophthalmology and internal medicine. General demographic data were collected from patients. An ophthalmologist examined all patients in terms of DR. A rheumatologist blinded to the clinical data performed NVC. The diameters of apical, arterial, and venous loop of capillaries were measured, and the microvascular changes of capillaries were scored. In this study, 44 patients with type 2 DM with DR (47.7% males) and 20 patients with type 2 DM without DR (55% males) were included. In our study, patients with type 2 DM with DR had more frequent capillary hemorrhage, more frequent ectasia, more frequent giant capillary, and more frequent neo-angiogenesis than patients with type 2 DM without DR. However, these findings were not statistically significant. Further controlled studies with large sample size are needed to determine the characteristic NVC findings of DR in patients with type 2 DM.


Surgical treatment of facial nerve involvement caused by leprosy.
Complete and partial nerve paralysis can result from leprosy. The latter is more prevalent and results in lagophthalmos and corneal hypoesthesia. The former is characterized by loss of facial expression, deviation of the face to the nonparalyzed side, difficulty in chewing, and drooling, in addition to lagophthalmos and corneal hypoesthesia. Affected patients are at risk to develop blindness, as well as suffering social and economic deprivation because of the effects of facial nerve paralysis. Prevention of blindness and amelioration of the latter were successfully achieved by muscle transfer procedures, temporalis transfer to the eyelid, and masseter transfer to the mouth and nasolabial fold in small, minimally equipped hospitals in Africa.


Antibacterial novel phenolic diterpenes from Podocarpus macrophyllus D. Don.
Two new sempervirol type diterpenes, inumakiols A, B, and six new totarol type diterpenes, inumakiols C-H, were isolated from a methanolic extract of bark of Podocarpus macrophyllus (Podocarpaceae), along with one known abietane, two known totarol type diterpenes, and one known totarol type diterpene dimer. The structures of the new compounds were elucidated by the spectroscopic methods. Some of them possessed antibacterial activity against oral pathogenic microorganisms with minimum inhibitory concentration (MIC) values ranging from 3.1 to 25 ppm.


A compact mirror manipulator in the SRRC beamline.
A compact mirror manipulator which has high stiffness and is easily adjustable has been developed for new beamlines at SRRC. It consists of a vertical stem to support the mirror and allows for six-axis precise positioning. The rotation adjustment is designed with a minimum of cross-coupling between adjustments. An independent support is fixed to the ground to reduce vibration from the chamber and the pump. Some performance test results in vacuum and in atmosphere, including vibration, repeatability, long-term drift etc., are described in this paper.


Gene expression by human monocytes from peripheral blood in response to exposure to metals.
With increasing life expectancy and active lifestyles, the longevity of arthroplasties has become an important problem in orthopaedic surgery and will remain so until novel approaches to joint preservation have been developed. The sensitivity of the recipient to the metal alloys may be one of the factors limiting the lifespan of implants. In the present study, the response of human monocytes from peripheral blood to an exposure to metal ions was investigated, using the method of real-time polymerase chain reaction (PCR)-based low-density arrays. Upon stimulation with bivalent (Co2+ and Ni2+) and trivalent (Ti3+) cations and with the calcium antagonist LaCl3, the strength of the elicited monocytic response was in the order of Co2+ > or = Ni2+ > Ti3+ > or = LaCl3. The transcriptional regulation of the majority of genes affected by the exposure of monocytes to Co2+ and Ni2+ was similar. Some genes critically involved in the processes of inflammation and bone resorption, however, were found to be differentially regulated by these bivalent cations. The data demonstrate that monocytic gene expression is adapted in response to metal ions and that this response is, in part, specific for the individual metals. It is suggested that metal alloys used in arthroplasties may affect the extent of inflammation and bone resorption in the peri-implant tissues in dependence of their chemical composition.


Predicting the functions and specificity of triterpenoid synthases: a mechanism-based multi-intermediate docking approach.
Terpenoid synthases construct the carbon skeletons of tens of thousands of natural products. To predict functions and specificity of triterpenoid synthases, a mechanism-based, multi-intermediate docking approach is proposed. In addition to enzyme function prediction, other potential applications of the current approach, such as enzyme mechanistic studies and enzyme redesign by mutagenesis, are discussed.


Folding control and unfolding free energy of yeast iso-1-cytochrome c bound to layered zirconium phosphate materials monitored by surface plasmon resonance.
The free energy change (Delta G degrees ) for the unfolding of immobilized yeast iso-1-cytochrome c (Cyt c) at nanoassemblies was measured by surface plasmon resonance (SPR) spectroscopy. Data show that SPR is sensitive to protein conformational changes, and protein solid interface exerts a major influence on bound protein stability. First, Cyt c was self-assembled on the Au film via the single thiol of Cys-102. Then, crystalline sheets of layered alpha-Zr(O(3)POH)(2).H(2)O (alpha-ZrP) or Zr(O(3)PCH(2)CH(2)COOH)(2).xH(2)O (alpha-ZrCEP) were adsorbed to construct alpha-ZrP/Cyt c/Au or alpha-ZrCEP/Cyt c/Au nanoassemblies. The construction of each layer was monitored by SPR, in real time, and the assemblies were further characterized by atomic force microscopy and electrochemical studies. Thermodynamic stability of the protein nanoassembly was assessed by urea-induced unfolding. Surprisingly, unfolding is reversible in all cases studied here. Stability of Cyt c in alpha-ZrP/Cyt c/Au increased by approximately 4.3 kJ/mol when compared to the unfolding free energy of Cyt c/Au assembly. In contrast, the protein stability decreased by approximately 1.5 kJ/mol for alpha-ZrCEP/Cyt c/Au layer. Thus, OH-decorated surfaces stabilized the protein whereas COOH-decorated surfaces destabilized it. These data quantitate the role of specific functional groups of the inorganic layers in controlling bound protein stability.


Development and validation of a high throughput whole blood thrombolysis plate assay.
The objective of this work was to develop a high throughput assay for testing in vitro the thrombolytic activity using citrated whole blood samples, and to overcome the limitations of currently available techniques. We successfully developed a method that involves forming halo shaped, tissue factor induced, whole blood clots in 96 well plates, and then precisely measuring the thrombolysis process with a spectrophotometer plate reader. We here describe the implementation of this novel method, which we refer to as halo assay, and its validation with plasmin, urokinase and tissue plasminogen activator at different doses. The resulting data is a highly detailed thrombolysis profile, allowing comparison of different fibrinolytic agents. The time point analysis allows kinetic data to be collected and calculated to determine key parameters such as the activation time and the rate of fibrinolysis. We also assessed the capacity of the model to study the effect of clot maturation time on the fibrinolytic rate, an aspect of thrombosis rather unexplored with currently available methods, but of increasing importance in drug development. This novel thrombolysis assay could be an extremely useful research tool; to study the complex process of thrombolysis, and a valuable translational clinical tool; as a screening device to rapidly identify hypo- or hyper-fibrinolysis.


Impact of cerebral collateral flow on stroke outcomes after carotid stenting.
Internal carotid artery stenosis is a main contributor to recurrent ischemic stroke. This study aimed to evaluate associations between recurrent stroke and changes in prestenting flow direction in the primary collaterals or both primary and secondary collaterals, and the potential interaction between extra- and intracranial arteries. This longitudinal study recruited stroke patients without intracranial stenosis who underwent right-side carotid stenting between 2011 and 2019. The main study outcome was recurrent stroke. Predictive factors were anterior circulation flow direction change (ACFDC), posterior circulation flow direction change, and reversal of ophthalmic artery/leptomeningeal anastomosis (ROALA) detected by transcranial color-coded duplex (TCCD) before carotid stenting. Patient follow-up was 9 years. Risk factors for recurrent stroke were identified by Kaplan-Meier plot and Cox regression analyses. A total of 234 patients (mean age 70.88 ± 10.3 years, 86.32% male) were included, and 115 had recurrent stroke. Kaplan-Meier plot showed that patients with left ACFDC and ROALA had worse outcomes than those with ACFDC only, while patients with left ACFDC had worse outcome than those with right ACFDC (both p < 0.001). Cox regression analysis showed that recurrent stoke was associated with ACFDC at right (hazard ratio [95% CI]: 20.988 [2.549-172.790], p < 0.01), left (151.441 [20.100-1140.993], p < 0.001), and both sides (144.889 [19.089-1099.710], p < 0.001). Anterior circulation flow direction change is significantly associated with recurrent stroke in patients with unilateral carotid stenosis. Patients with ACFDC and ROALA together have worse outcomes compared to those with ACFDC only. Prestenting TCCD images help provide definitive information to predict outcomes after carotid stenting.


Effectiveness of Strengthening RC Beams Using Composite Materials-An Accelerated Strengthening Method.
The article analyses the results obtained from tests of preloaded reinforced concrete beams strengthened with carbon fibre strips bonded into the concrete reinforcement cover (NSMR method). Adhesive (thixotropic epoxy resin) bonding takes 7 days at 23 °C. The strengthening process was accelerated by heating the strip using a prototype heating device. Tests on the reinforced concrete members confirmed that accelerating the strengthening process is feasible and allowed the selection of the optimal heating temperature to provide the greatest strengthening level. The study primarily aimed to analyse the effectiveness of strengthening applied to the bottom of reinforced concrete beams under sustained loading throughout the adhesive curing process, simulating real conditions on site. Significantly higher strengthening efficiency was achieved with the use of strip heating, which accelerated adhesive cure time and reduced the strengthening execution time from 7 days to 1.5 h. The analysis included the evaluation of the effect of the steel and composite reinforcement ratios on strengthening effectiveness.


Universal detection of hepatitis E virus by two real-time PCR assays: TaqMan and Primer-Probe Energy Transfer.
Hepatitis E virus (HEV) is a major cause of food- and waterborne diseases in countries with poor sanitation. Furthermore, travellers to such countries are also at risk of contracting the virus. Noteworthily, during the last decade an increasing number of non-travel-related cases were recorded even in countries with high sanitary standards. An alternative, direct route of infection, from animals to humans (zoonotic transmission) is suspected to be the cause of recent cases of hepatitis E. In order to provide rapid and sensitive methods for detecting the virus in various hosts, two real-time PCR methods were developed and compared: a TaqMan and Primer-Probe Energy Transfer (PriProET) assay. These highly sensitive novel methods provide valuable diagnostic tools to investigate zoonotic transmission, to detect the virus in the food chain and in research related to the potential of hepatitis E virus to cross the species barrier. The results show that the two novel PCR assays are robust, highly sensitive and specific for broad range detection of the four genotypes of HEV. Compared to PriProET, the TaqMan assay appears to perform slightly better, with higher fluorescence values for positive samples. However, the PriProET has the benefit of better tolerating the point mutations in the target nucleic acids. Thus, it provides a more powerful tool to detect new virus variants. These new molecular diagnostic assays are practical tools that can be employed in the area of public health, for disease diagnosis and for tracking outbreaks. In basic research the methods provide new tools to study HEV biology, including virus-host interactions and transmission between various host species.


Social climate within an adolescent medium-secure facility.
The objectives of the study were to investigate the social climate of two different types of units (open vs. secure) contained within the same South London adolescent medium-secure facility. Two hypotheses were generated: (a) adolescents would rate the social climate of the whole facility in a more negative direction than staff and (b) adolescents and staff would rate the social climate of the open units in a more positive direction than the social climate of the secure units. 43 adolescents and 49 staff members from the open units and the secure units were recruited and completed the Correctional Institutions Environment Scale (CIES), a measure of social climate. Overall, adolescents tended to rate the facility in a more negative direction. All participants rated the open units in a more positive direction than secure units. However, on selected subscales there were differences. The findings of this study suggest that adolescents and staff may perceive their shared social climate differently. This may have implications for those attempting to develop positive social climates within secure services.


Characterization of cell lines developed from the glassy-winged sharpshooter, Homalodisca coagulata (Hemiptera: Cicadellidae).
Four continuous cell lines were established from the embryos of the glassy-winged sharpshooter, Homalodisca coagulata (Say), an economically important insect vector of bacterial pathogens of grape, almond, citrus, oleander, and other agricultural and ornamental plantings. The cell lines were designated GWSS-Z10, GWSS-Z15, GWSS-G3, and GWSS-LH. The GWSS-Z10, GWSS-Z15, and GWSS-G3 lines were cultured in Ex-Cell 401 medium supplemented with 10% fetal bovine serum (FBS), whereas the GWSS-LH line was cultured in LH medium supplemented with 20% FBS. The cell lines were characterized in terms of their morphology, growth, protein composition, and polymerase chain reaction- amplification patterns of their chromosomal deoxyribonucleic acid. The population doubling times of GWSS-Z10, GWSS-Z15, GWSS-G3, and GWSS-LH were 46.2, 90.9, 100.3, and 60.2 h, respectively. These lines should be useful for the study of insect-pathogenic viruses of leafhoppers, aphids, treehoppers, and other related insects as well as plant-pathogenic viruses that are transmitted by these insects.


Treatment of Cirrhosis-Associated Hyponatremia with Midodrine and Octreotide.
Hyponatremia in the setting of cirrhosis is a common electrolyte disorder with few therapeutic options. The free water retention is due to non-osmotic vasopressin secretion resulting from the cirrhosis-associated splanchnic vasodilatation. Therefore, vasoconstrictive therapy may correct this electrolyte abnormality. The aim of this study was to assess the efficacy of midodrine and octreotide as a therapeutic approach to increasing urinary electrolyte-free water clearance (EFWC) in the correction of cirrhosis-associated hyponatremia. This observational study consisted of 10 patients with cirrhosis-associated hyponatremia. Hypovolemia was ruled out as the cause of the hyponatremia with a 48-h albumin challenge (25 g IV q6 h). Patients whose hyponatremia failed to improve with albumin challenge were started on midodrine and octreotide at 10 mg po tid and 100 μg sq tid, respectively, with rapid up-titration as tolerated to respective maximal doses of 15 mg tid and 200 μg tid within the first 24 h. We assessed urinary EFWC and serum sodium concentration before and 72 h after treatment. Pretreatment serum sodium levels ranged from 119 to 133 mmol/L. The mean pretreatment serum sodium concentration ± SEM was 124 mmol/L ± 1.6 vs 130 mmol/L ± 1.5 posttreatment (p = 0.00001). The mean pretreatment urinary EFWC ± SEM was 0.33 L ± 0.07 vs 0.82 L ± 0.11 posttreatment (p = 0.0003). Our data show a statistically significant increase in serum sodium concentration and urinary EFWC with the use of midodrine and octreotide in the treatment of cirrhosis-associated hyponatremia.


[The efficacy and safety of ultrafiltration for patients with heart failure: results from a single-center randomized controlled study].
Objective: To evaluate the efficacy and safety of ultrafiltration in patients with heart failure. Methods: One hundred and thirty four cases of patients with heart failure, who hospitalized in our hospital from June 2010 to June 2016 were enrolled in this study. Random serial number was generated using SPSS 22.0 software, patients were then randomly divided into control group and ultrafiltration group with the proportion of 1∶1 (67 cases in each group). Patients in the control group received standard therapy. Patients in the ultrafiltration group received ultrafiltration therapy for 8 hours. Curative effect was evaluated after 8 hours treatment in the control group and after 12 hours in the ultrafiltration group. Following parameters were compared between the two groups: body weight, dyspnea score and 6 minutes walking distance as well as blood pressure, heart rate, Na(+) , K(+) , Cl(-), pH, HCO(3)(-), Hb, PLT, Cr, BUN levels. Results: (1)Two patients died during run-in process and eventually 132 cases were chosen for final analysis (65 cases in control group and 67 cases in the ultrafiltration group). Gender, age, type of heart failure, dyspnea score, body weight at baseline were similar between the two groups. (2)Post therapy, patients' body weight decreased obviously, while dyspnea score and 6 minutes walking distance increased significantly in the ultrafiltration group compared to baseline(all P<0.05), and the improvement was significantly greater compared to control group(all P<0.05). (3)The safety index comparison of two groups: blood pressure, heart rate, Na(+) , K(+) , Cl(-), pH, HCO(3)(-), Hb, PLT, Cr, and BUN were similar between the two groups at baseline and post therapy. Conclusion: Ultrafiltration therapy is safe and effective to treat patients with heart failure.


Morning symptoms in COPD: a treatable yet often overlooked factor.
Chronic obstructive pulmonary disease (COPD) patients experience the morning as the worst period of the day. Nevertheless, morning symptoms are not mentioned in COPD guidelines. Areas covered: Different topics on morning symptoms are covered in this review to underline their importance: occurrence, tools for assessment and therapies to limit morning symptoms. Expert commentary: Morning symptoms are common and have a negative influence on a patient's life. Pharmacotherapy seems to be effective in decreasing morning symptoms. A validated tool to assess morning symptoms is lacking. Therefore, more research should focus on assessing morning symptoms with a validated tool to further prove the effect of (pharmaco-) therapy. This will hopefully result in inclusion of morning symptoms in future guidelines.


Viroid research and its significance for RNA technology and basic biochemistry.
Viroids were described 47 years ago as the smallest RNA molecules capable of infecting plants and autonomously self-replicating without an encoded protein. Work on viroids initiated the development of a number of innovative methods. Novel chromatographic and gelelectrophoretic methods were developed for the purification and characterization of viroids; these methods were later used in molecular biology, gene technology and in prion research. Theoretical and experimental studies of RNA folding demonstrated the general biological importance of metastable structures, and nuclear magnetic resonance spectroscopy of viroid RNA showed the partially covalent nature of hydrogen bonds in biological macromolecules. RNA biochemistry and molecular biology profited from viroid research, such as in the detection of RNA as template of DNA-dependent polymerases and in mechanisms of gene silencing. Viroids, the first circular RNA detected in nature, are important for studies on the much wider spectrum of circular RNAs and other non-coding RNAs.


Reliability of a novel neurostimulation method to study involuntary muscle phenomena.
Experimental methods involving painful electrical stimulation of a peripheral nerve showed the existence of a minimum stimulation frequency capable of inducing cramp, termed "threshold frequency" (TF). Our aim was to test an alternative method to induce fasciculations and cramps electrically. Two daily sessions of electrical stimulation of the abductor hallucis muscle were performed in 19 volunteers on 3 days: stimulation trains of 150 monophasic square pulses (duration 152 micros) of increasing frequency (current intensity 30% higher than maximal; frequency of the first trial, 4 pps; recovery between trials, 1 min) were delivered to the main muscle motor point until a cramp developed. Once a cramp was induced the protocol was repeated after 30 min. To verify by electromyography that cramp occurred, a surface electrode array was placed between the motor point and the distal tendon. Ambient and skin temperature were kept constant in all sessions. Fasciculations and cramps were elicited in all subjects. We observed the following median (interquartile range) values of TF: day 1 (session 1), 13 (6) pps; day 1 (session 2), 16 (4) pps; day 2 (session 1), 16 (6) pps; day 2 (session 2), 18 (6) pps; day 3 (session 1), 17 (4) pps; day 3 (session 2), 18 (8) pps. TF intersession intraclass correlation coefficients were 0.82, 0.92, and 0.90 for days 1, 2, and 3, respectively. TF interday intraclass correlation coefficient was 0.85. The absence of pain due to the stimulation and the demonstration of TF reliability support the use of our method for the study of involuntary muscle phenomena.


Endoscopic management of biliary obstruction caused by cavernous transformation of the portal vein.
Symptomatic biliary obstruction caused by cavernous transformation of the portal vein is an extremely rare disorder for which there is no consensus as to optimal treatment. The results of endoscopic treatments in a small group of patients is reviewed. A total of 10 patients (5 men, 5 women; mean age 36.1 years, range 17-48 years) with severe biliary strictures were treated between 1995 and 2001. Biliary sphincterotomy was performed in all patients. Four patients also underwent balloon dilation, nasobiliary drainage, and stone or sludge extraction by using a balloon. All patients had stent insertion. The mean duration of therapy was 3.3 years (range 1-7 years). There was no complication directly related to the endoscopic procedures except for hemobilia that occurred in one patient during stent removal. Cholangitis developed in 5 patients during the therapy period and was treated endoscopically. In 4 patients, significant improvement in the biliary stricture was observed and stents were removed in 3. These patients were followed without stent insertion for one year. Endoscopic management of biliary stricture caused by cavernous transformation of the portal vein appears to be effective and safe.


Polyhydrides of Platinum Group Metals: Nonclassical Interactions and σ-Bond Activation Reactions.
The preparation, structure, dynamic behavior in solution, and reactivity of polyhydride complexes of platinum group metals, described during the last three decades, are contextualized from both organometallic and coordination chemistry points of view. These compounds, which contain dihydrogen, elongated dihydrogen, compressed dihydride, and classical dihydride ligands promote the activation of B-H, C-H, Si-H, N-H, O-H, C-C, C-N, and C-F, among other σ-bonds. In this review, it is shown that, unlike other more mature areas, the chemistry of polyhydrides offers new exciting conceptual challenges and at the same time the possibility of interacting with other fields including the conversion and storage of regenerative energy, organic synthetic chemistry, drug design, and material science. This wide range of possible interactions foresees promising advances in the near future.


Effects of experimental muscle pain on muscle activity and co-ordination during static and dynamic motor function.
The relation between muscle pain, muscle activity, and muscle co-ordination is still controversial. The present human study investigates the influence of experimental muscle pain on resting, static, and dynamic muscle activity. In the resting and static experiments, the electromyography (EMG) activity and the contraction force of m. tibialis anterior were assessed before and after injection of 0.5 ml hypertonic saline (5%) into the same muscle. In the dynamic experiment, injections of 0.5 ml hypertonic saline (5%) were performed into either m. tibialis anterior (TA) or m. gastrocnemius (GA) and the muscle activity and co-ordination were investigated during gait on a treadmill by EMG recordings from m. TA and m. GA. At rest no evidence of EMG hyperactivity was found during muscle pain. The maximal voluntary contraction (MVC) during muscle pain was significantly lower than the control condition (P < 0.05). During a static contraction at 80% of the pre-pain MVC muscle pain caused a significant reduction in endurance time (P < 0.043). During dynamic contractions, muscle pain resulted in a significant decrease of the EMG activity in the muscle, agonistic to the painful muscle (P < 0.05), and a significant increase of the EMG activity of the muscle, antagonistic to the painful muscle (P < 0.05). Muscle pain seems to cause a general protection of painful muscles during both static and dynamic contractions. The increased EMG activity of the muscle antagonistic to the painful muscle is probably a functional adaptation of muscle co-ordination in order to limit movements. Modulation of muscle activity by muscle pain could be controlled via inhibition of muscles agonistic to the movement and/or excitation of muscles antagonistic to the movement. The present results are in accordance with the pain-adaptation model (Lund, J.P., Stohler, C.S. and Widmer, C.G. In: H. Vaerøy and H. Merskey (Eds.), Progress in Fibromyalgia and Myofascial Pain. Elsevier, Amsterdam, 1993, pp. 311-327.) which predicts increased activity of antagonistic muscle and decreased activity of agonistic muscle during experimental and clinical muscle pain.


Microsatellite diversity and genetic structure of fragmented populations of the rare, fire-dependent shrub Grevillea macleayana.
Recent habitat loss and fragmentation superimposed upon ancient patterns of population subdivision are likely to have produced low levels of neutral genetic diversity and marked genetic structure in many plant species. The genetic effects of habitat fragmentation may be most pronounced in species that form small populations, are fully self-compatible and have limited seed dispersal. However, long-lived seed banks, mobile pollinators and long adult lifespans may prevent or delay the accumulation of genetic effects. We studied a rare Australian shrub species, Grevillea macleayana (Proteaceae), that occurs in many small populations, is self-compatible and has restricted seed dispersal. However, it has a relatively long adult lifespan (c. 30 years), a long-lived seed bank that germinates after fire and is pollinated by birds that are numerous and highly mobile. These latter characteristics raise the possibility that populations in the past may have been effectively large and genetically homogeneous. Using six microsatellites, we found that G. macleayana may have relatively low within-population diversity (3.2-4.2 alleles/locus; Hexp = 0.420-0.530), significant population differentiation and moderate genetic structure (FST = 0.218) showing isolation by distance, consistent with historically low gene flow. The frequency distribution of allele sizes suggest that this geographical differentiation is being driven by mutation. We found a lack mutation-drift equilibrium in some populations that is indicative of population bottlenecks. Combined with evidence for large spatiotemporal variation of selfing rates, this suggests that fluctuating population sizes characterize the demography in this species, promoting genetic drift. We argue that natural patterns of pollen and seed dispersal, coupled with the patchy, fire-shaped distribution, may have restricted long-distance gene flow in the past.


Design, synthesis and biological evaluation of a new bridged immunosuppressor.
A bridged peptide with the sequence: H-Thr-Pro-Gln-Arg-Gly-Asp-Val-gamma-Abu-Asn-Asp-Gln-Glu-Glu-Thr-Thr-Gly-Val-Val-Ser-Thr-Pro-Leu-Ile-Arg-Asn-Gly-OH was designed to mimic the discontinuous epitope of the HLA-DQ molecule that might interact with CD4. The bridged peptide revealed distinct suppressory effect in the humoral immune response. This result supports our suggestion that the 164-172 region of the HLA-DQ molecule may enhance its interactions with coreceptors, possibly with CD4.


Long non‑coding RNAs, lipid metabolism and cancer (Review).
Cancer has emerged as the most common cause of death in China. The change in lipid metabolism has been confirmed to have a role in several tumor types, such as esophageal, gastric, colorectal and liver cancer. Cancer cells use lipid metabolism for energy and then rapidly proliferate, invade and migrate. The main pathway by which cancer cell lipid metabolism influences cancer progression is increased fatty acid synthesis. Long non-coding (lnc)RNAs are important ncRNAs that were indicated to have significant roles in the development of human tumors. They are considered potential tumor biomarkers. Increased lipid synthesis or uptake due to deregulation of lncRNAs contributes to rapid tumor growth. In the present review, current studies on the relationship between lncRNAs, lipid metabolism and the occurrence and development of tumors were collated and summarized, and their mechanism of action was discussed. The review is expected to provide a theoretical basis for tumor treatment and prognosis evaluation based on the effective regulation of lncRNAs and lipid metabolism.


A Study of Mycobacterium tuberculosis Detection Using Different Neural Networks in Autopsy Specimens.
Tuberculosis (TB) presents a substantial health risk to autopsy staff, given its three to five times higher incidence of TB compared to clinical staff. This risk is notably accentuated in South Korea, which reported the highest TB incidence rate and the third highest TB mortality rate among OECD member countries in 2020. The standard TB diagnostic method, histopathological examination of sputum or tissue for acid-fast bacilli (AFB) using Ziehl-Neelsen staining, demands microscopic examination of slides at 1000× magnification, which is labor-intensive and time-consuming. This article proposes a computer-aided diagnosis (CAD) system designed to enhance the efficiency of TB diagnosis at magnification less than 1000×. By training nine neural networks with images taken from 30 training slides and 10 evaluation slides at 400× magnification, we evaluated their ability to detect M. tuberculosis. The N model achieved the highest accuracy, with 99.77% per patch and 90% per slide. We discovered that the model could aid pathologists in preliminary TB screening, thereby reducing diagnostic time. We anticipate that this research will contribute to minimizing autopsy staff's infection risk and rapidly determining the cause of death.


Assessment of coastal vulnerability through the use of GIS tools in South Sicily (Italy).
This study assessed coastal erosion vulnerability along a 90-km sector, which included both erosional and accretionary beaches, and different levels of human occupation. Two aerial photogrammetric flights were used to reconstruct coastal evolution between 1977 and 1999. During this period, extensive accretion was recorded updrift of human structures at harbors and ports, e.g., Scoglitti (105.6 m), Donnalucata (52.8 m), and Pozzallo (94.6 m). Conversely, erosion was recorded in downdrift areas, with maximum values at Modica Stream mouth (63.8 m) and Point Castellazzo (35.2 m). Assessments were subsequently divided into four categories ranging from "high erosion" to "accretion." Several sources were examined to assess human activities and land use. The latter was mapped and divided into four categories, ranging from "very high" to "no capital" land use. Subsequently, coastal erosion vulnerability was assessed by combining land use categories with recorded coastline behavior. Results showed "very high" to "high" vulnerability along 5.8% and 16.6%, respectively, of the littoral, while 20.9% and 56.7%, respectively, was found to exhibit "medium" and "low/very low" vulnerability. A very good agreement between predicted coastal vulnerability and coastal trend had been observed over recent years. Furthermore, several human structures and activities are located within the "imminent collapse zone (ICZ)" which reached maximum values of 17.5 m at Modica Stream and 13.5 m at Point Braccetto.


A De Novo Nonsense Mutation in MAGEL2 in a Patient Initially Diagnosed as Opitz-C: Similarities Between Schaaf-Yang and Opitz-C Syndromes.
Opitz trigonocephaly C syndrome (OTCS) is a rare genetic disorder characterized by craniofacial anomalies, variable intellectual and psychomotor disability, and variable cardiac defects with a high mortality rate. Different patterns of inheritance and genetic heterogeneity are known in this syndrome. Whole exome and genome sequencing of a 19-year-old girl (P7), initially diagnosed with OTCS, revealed a de novo nonsense mutation, p.Q638*, in the MAGEL2 gene. MAGEL2 is an imprinted, maternally silenced, gene located at 15q11-13, within the Prader-Willi region. Patient P7 carried the mutation in the paternal chromosome. Recently, mutations in MAGEL2 have been described in Schaaf-Yang syndrome (SHFYNG) and in severe arthrogryposis. Patient P7 bears resemblances with SHFYNG cases but has other findings not described in this syndrome and common in OTCS. We sequenced MAGEL2 in nine additional OTCS patients and no mutations were found. This study provides the first clear molecular genetic basis for an OTCS case, indicates that there is overlap between OTCS and SHFYNG syndromes, and confirms that OTCS is genetically heterogeneous. Genes encoding MAGEL2 partners, either in the retrograde transport or in the ubiquitination-deubiquitination complexes, are promising candidates as OTCS disease-causing genes.


Free synthetic and natural estrogen hormones in influent and effluent of three municipal wastewater treatment plants.
Three municipal wastewater treatment plants (WWTPs) in southeastern Pennsylvania were sampled to determine the presence and concentrations of 12 natural and synthetic estrogen hormones in the wastewater influent and effluent. The target estrogens were 17alpha-estradiol, estrone, estriol, equilin, 17alpha-dihydroequilin, 17beta-estradiol, 17alpha-ethinyl estradiol, gestodene, norgestrel, levonorgestrel, medrogestone, and trimegestone. One WWTP uses a biofilm reactor (packed-bed trickling filter),and the other two use suspended-growth media (continuously stirred activated sludge reactor and sequential batch reactor). Estrone was detected in all the three plants; estriol and estradiol were detected at two WWTPs; and 17 alpha-dihydroequilin and 17 alpha-ethinyl estradiol were detected at one WWTP. The concentration of estrogens in the influent and effluent of the three treatment plants ranged from 1.2 to 259 ng/L and 0.5 to 49 ng/L, respectively. The percentage removal of estrogens from the aqueous phase ranged from 41 to 99%, except in the case of 17alpha-dihydroequilin; the removal of 17alpha-dihydroequilin was negligible. The suspended-growth media systems showed higher removal efficiencies for estrogens than the biofilm system. The analytical method uses a Varian C-18 solid-phase extraction (Varian Inc., Palo Alto, California), followed by a derivatization with bis(trimethylsilyl)trifluoroacetamide. The detection limits for the estrogen compounds ranged from 0.1 to 10 ng/L using a sample size of 1 L. The method recoveries ranged from 71 to 120%, and the relative standard deviation ranged from 6 to 14% for all the hormones.


Impaired autophagy triggered by HDAC9 in mesenchymal stem cells accelerates bone mass loss.
Bone mass loss in aging is linked with imbalanced lineage differentiation of bone marrow mesenchymal stem cells (BMMSCs). Recent studies have proved that histone deacetylases (HDACs) are regarded as key regulators of bone remodeling. However, HDACs involve in regulating BMMSC bio-behaviors remain elusive. Here, we investigated the ability of HDAC9 on modulation of autophagy and its significance in lineage differentiation of BMMSCs. The effects of HDAC9 on lineage differentiation of BMMSCs and autophagic signaling were assessed by various biochemical (western blot and ChIP assay), morphological (TEM and confocal microscopy), and micro-CT assays. Sixteen-month mice manifested obvious bone mass loss and marrow fat increase, accompanied with decreased osteogenic differentiation and increased adipogenic differentiation of BMMSCs. Further, the expression of HDAC9 elevated in bone and BMMSCs. Importantly, HDAC9 inhibitors recovered the lineage differentiation abnormality of 16-month BMMSCs and reduced p53 expression. Mechanistically, we revealed that HDAC9 regulated the autophagy of BMMSCs by controlling H3K9 acetylation in the promoters of the autophagic genes, ATG7, BECN1, and LC3a/b, which subsequently affected their lineage differentiation. Finally, HDAC9 inhibition improved endogenous BMMSC properties and promoted the bone mass recovery of 16-month mice. Our data demonstrate that HDAC9 is a key regulator in a variety of bone mass by regulating autophagic activity in BMMSCs and thus a potential target of age-related bone loss treatment.


Treatment Decision-Making in Metastatic Prostate Cancer: Perceptions of Locus of Control Among Patient, Caregiver, and Physician Triads.
Multiple treatments for metastatic prostate cancer have similar efficacy, leaving patients with complicated treatment choices. Shared decision-making can facilitate difficult treatment decisions, but the extent to which this is used for metastatic prostate cancer is unknown. We assessed patient, caregiver, and physician perceptions of decision locus of control (shared decision-making vs physician- or patient-directed decisions) and the degree of agreement between groups. Triads of patients, caregivers, and physicians completed surveys of decision-making practices after a clinic visit in which a decision occurred. To evaluate the degree of agreement for decision locus of control, we used the quadratic-weighted kappa coefficient (κ). We used relative frequencies to evaluate which knowledge learned and treatment factors were most strongly endorsed by patients as informing and influencing their treatment decision-making, respectively. Fifty triads participated, with median patient age of 72 years. A majority of patients, caregivers, and physicians reported shared decision-making (66%, 56%, and 52%, respectively). Patients and physicians demonstrated minimal agreement about decision locus of control (44%, κ=0.35 [SD = 0.52]), but caregiver reports were not statistically significantly associated with physician and patient reports (38%, κ=0.23, [SD = 0.28]), p=0.055; 44%, κ=0.34 [SD = 1.98], p=0.14). Treatment efficacy was the most common patient-reported factor influencing treatment decisions (44%). This study characterized metastatic prostate cancer patients', caregivers', and physicians' experiences and communication preferences for treatment decision-making. Patients and physicians had greater agreement in decision locus of control compared with caregivers, yet patient-physician agreement was minimal. Metastatic prostate cancer patients report being influenced by information about treatment efficacy and clear next steps, and a desire for patient-friendly language and an invitation to be as involved in decision making at their preferred level. Emphasizing these may increase agreement in decision locus of control between all participants in the decision-making process.


Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study.
To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). A 12-month, multicenter, randomized, double-masked, active-controlled, phase IIIb study. Patients with primary or recurrent subfoveal CNV secondary to AMD (353 patients), with predominantly classic, minimally classic, or occult (no classic component) lesions. Patients were randomized (1:1:1) to 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised of a loading phase (3 consecutive monthly injections) followed by a 9-month maintenance phase (either monthly or quarterly injection). Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 12 and the incidence of adverse events (AEs). In the per-protocol population (293 patients), BCVA, measured by Early Treatment Diabetic Retinopathy Study-like charts, increased from baseline to month 12 by 4.9, 3.8, and 8.3 letters in the 0.3 mg quarterly (104 patients), 0.5 mg quarterly (88 patients), and 0.3 mg monthly (101 patients) dosing groups, respectively. Similar results were observed in the intent-to-treat (ITT) population (353 patients). The mean decrease in CRT from baseline to month 12 in the ITT population was -96.0 μm in 0.3 mg quarterly, -105.6 μm in 0.5 mg quarterly, and -105.3 μm in 0.3 mg monthly group. The most frequent ocular AEs were conjunctival hemorrhage (17.6%, pooled quarterly groups; 10.4%, monthly group) and eye pain (15.1%, pooled quarterly groups; 20.9%, monthly group). There were 9 ocular serious AEs and 3 deaths; 1 death was suspected to be study related (cerebral hemorrhage; 0.5 mg quarterly group). The incidences of key arteriothromboembolic events were low. After 3 initial monthly ranibizumab injections, both monthly (0.3 mg) and quarterly (0.3 mg/0.5 mg) ranibizumab treatments maintained BCVA in patients with CNV secondary to AMD. At month 12, BCVA gain in the monthly regimen was higher than that of the quarterly regimens. The noninferiority of a quarterly regimen was not achieved with reference to 5.0 letters. The safety profile was similar to that reported in prior ranibizumab studies.


Increased thalamocortical connectivity to the medial prefrontal cortex with recovery of impaired consciousness in a stroke patient: A case report.
We report a stroke patient who showed increased thalamocortical connectivity to the medial prefrontal cortex (mPFC) with recovery of impaired consciousness that was demonstrated on diffusion tensor tractography (DTT) of the ascending reticular activating system (ARAS). A 48-year-old male patient underwent craniectomy and hematoma removal for spontaneous intracerebral hemorrhage in the right basal ganglia and thalamus. When he started rehabilitation at 5 weeks after onset he was in a vegetative state with a Coma Recovery Scale-Revised score of 6. The patient was diagnosed spontaneous intracerebral hemorrhage in the right basal ganglia and thalamus. He underwent comprehensive rehabilitation including neurotropic durgs, transcranial direct current stimulation, and repetitive transcranial magnetic stimulation of the left prefrontal lobe (Brodmann area 10). After 5 weeks of rehabilitation, the patient had recovered to a nearly normal conscious state with a Coma Recovery Scale-Revised score of 22. On 10-week DTT, thickening of the lower dorsal ARAS was observed on both sides compared with 5-week DTT. Decreased neural connectivity to the left PFC was observed on 5-week DTT whereas decreased neural connectivity to the left PFC was increased on 10-week DTT, especially the mPFC. Increased thalamocortical connectivity to the mPFC was demonstrated in a stroke patient who showed concomitant recovery from a vegetative state to a nearly normal conscious state. The results suggest that the increased neural connectivity to the mPMC contributed to recovery of consciousness in this patient.


Spontaneous vesicle formation of single chain and double chain cationic surfactant mixtures.
The concentration vs composition diagram of aggregate formation of the dodecyltrimethylammonium bromide (DTAB) and didodecyldimethylammonium bromide (DDAB) mixture in aqueous solution at rather dilute region was constructed by analyzing the surface tension, turbidity, and electrical conductivity data and inspected by cryo-TEM images and dynamic light scattering data. Although the aqueous solution of DTAB forms only micelles, the transition from monomer to small aggregates and then to vesicle was found at 0.1 < X2 <or=1, where X2 is the mole fraction of DDAB in the DTAB-DDAB mixture, while vesicle particles were formed directly from monomer solution at 0 < X2 < 0.1. Furthermore, the transition from vesicle to micelle was found at 0 < X2 < 0.4 at higher concentrations. An addition of DTAB to DDAB solution lowered considerably the DDAB concentration of the vesicle formation, which is attributable to asymmetric distribution of DTAB molecules between inner and outer monolayers of the vesicle bilayer. The shape and size of aggregates were obtained from surface tension, cryo-TEM, and light scattering data.


Estimation of IgG and IgM brucella antibodies in infected and non-infected persons by a radioimmune technique.
Sera from 105 blood donors and eight patients with brucellosis were examined for anti-brucella IgG and IgM by a radioimmune technique. A pooled standard was used for comparison and evaluation. The upper limit of the 99% confidence interval on the mean of both immunoglobulin classes in blood donor sera was below 7 units/ml. Antibody response was shown in three acute, two relapsing, two chronic, and one asymptomatic cases. Values of up to 300 units/ml of both classes were found in the acute cases. Chronic sufferers showed lower concentrations of antibody. Relapsing cases showed increases comprising mainly IgG. The assay method, which shows general concordance with the results of conventional tests. is useful and measures individual immunoglobulin classes directly.


Caring with comfort rooms. Reducing seclusion and restraint use in psychiatric facilities.
The reduction of seclusion and restraint is a national patient safety focus in psychiatric settings. Studies have demonstrated that multisensory or comfort rooms contribute to higher consumer satisfaction and lower rates of seclusion and restraint in general hospitals. As an alternative to the traditionally uncomfortable time-out room, a comfort room was constructed on an acute adult inpatient unit. This space was designed with comfortable furniture, soothing colors, soft lighting, quiet music, and other sensory aids to help reduce unsettled patients' level of stress. The frequency and duration of seclusion and restraint use on the pilot unit was studied before and after implementation of the comfort room. The use of seclusion and restraint was also compared with a similar admission unit without a comfort room. Results supported the hypothesis that the presence of a comfort room significantly reduced seclusion and restraint, and that the use of the comfort room helped reduce patients' stress.


Overview of equilibrium reconstruction on DIII-D using new measurements from an expanded motional Stark effect diagnostic.
Motional Stark effect (MSE) measurements constrain equilibrium reconstruction of DIII-D tokamak plasmas using the equilibrium code EFIT. In 2007, two new MSE arrays were brought online, bringing the system to three core arrays, two edge arrays, and 64 total channels. We present the first EFIT reconstructions using this expanded system. Safety factor and E(R) profiles produced by fitting to data from the two new arrays and one of the other three agree well with independent measurements. Comparison of the data from the three arrays that view the core shows that one of the older arrays is inconsistent with the other two unless the measured calibration factors for this array are adjusted. The required adjustments depend on the toroidal field and plasma current direction, and on still other uncertain factors that change as the plasma evolves. We discuss possible sources of calibration error for this array.


Evaluation of electron capture detection in reversed-phase HPLC for pharmaceutical analysis.
The coupling of RP-LC to electron capture detection (ECDNi(63)) is described. To reduce the amount of mobile phase entering into the detector, interfacing was performed via a Scott-type spray chamber. The performance of RP-LC/ECDNi(63) was evaluated for pharmaceutical analysis and the results show that the system is able to work in a routine environment using columns with 2 mm id and common amounts of the organic modifiers methanol or ACN in the mobile phase. Because of the high sensitivity and selectivity toward electrophilic compounds, the use of this detector opens possibilities for the analysis of impurities down to the 0.05% level of active pharmaceutical ingredients (API).


Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis.
The transcription factors signal transducer and activator of transcription (STAT)1 and T-bet control the differentiation of interferon (IFN)-gamma-producing T helper type (Th)1 cells. Here we compare the role of T-bet and STAT1 in the initiation and regulation of experimental autoimmune encephalomyelitis (EAE), a disease initiated by Th1 cells. T-bet-deficient mice immunized with myelin oligodendrocyte glycoprotein (MOG) were resistant to the development of EAE. This protection was also observed when T-bet(-/-) mice were crossed to the MOG-specific 2D2 T cell receptor transgenic strain. In contrast, although T-bet is downstream of STAT1, STAT1(-/-) mice were highly susceptible to EAE and developed more severe and accelerated disease with atypical neuropathologic features. The function of T-bet was dominant as mice deficient in both T-bet and STAT1 were also protected from EAE. CD4(+) CD25(+) regulatory T cells from these two mice strains were fully competent and do not explain the difference in disease susceptibility. However, enhanced EAE in STAT1(-/-) mice was associated with continued generation of IFN-gamma-producing Th1 cells and up-regulation of selective chemokines responsible for the increased recruitment of macrophages and neutrophils in the central nervous system. Although the two transcription factors, STAT1 and T-bet, both induce IFN-gamma gene transcription, our results demonstrate marked differences in their function in regulating pathogenic Th1 cell responses.


Effect of Probiotics for the Prevention of Acute Radiation-Induced Diarrhoea Among Cervical Cancer Patients: a Randomized Double-Blind Placebo-Controlled Study.
Radiotherapy is the mainstay treatment of cervical cancer and the most common acute side effect is radiation-induced diarrhoea (RID), which can affect up to 80% of the patients. The most frequently used probiotics for the RID in previous studies with somewhat positive results are Lactobacillus and Bifidobacterium strains. This study was aimed to investigate the effect of a probiotic containing live Lactobacillus acidophilus LA-5 plus Bifidobacterium animalis subsp. lactis BB-12 for the prevention of acute (RID) among cervical cancer patients. Patients receiving external beam pelvic radiotherapy with or without concurrent chemotherapy were randomized into probiotic or placebo groups and were double-blinded. The probiotic group received the capsules containing 1.75 billion lyophilized live bacteria to be taken one capsule three times daily beginning from the first day until the end of radiotherapy, and the placebo group received identically appearing capsules containing starch with the same schedule. Every patient received the standard dietary recommendations. The patients were assessed daily during radiotherapy and follow-up weekly for 3 weeks after radiotherapy. Total 54 patients were analyzed. The incidence of diarrhoea was reduced in the probiotic group than the placebo group (53.8 and 82.1%, p < 0.05). The mild-to-moderate and severe diarrhoea were significantly reduced in the probiotic group (p < 0.05). The use of loperamide as an anti-diarrhoeal medication was significantly reduced in the probiotic group than the placebo group (p < 0.01). The difference in grade 2 abdominal pain and episodes of abdominal pain in days were also significant (p < 0.001). Therefore, supplementation of probiotic is an easy and effective way to reduce the incidence and severity of RID in cervical cancer patients.


HfSe2 thin films: 2D transition metal dichalcogenides grown by molecular beam epitaxy.
In this work, we demonstrate the growth of HfSe2 thin films using molecular beam epitaxy. The relaxed growth criteria have allowed us to demonstrate layered, crystalline growth without misfit dislocations on other 2D substrates such as highly ordered pyrolytic graphite and MoS2. The HfSe2 thin films exhibit an atomically sharp interface with the substrates used, followed by flat, 2D layers with octahedral (1T) coordination. The resulting HfSe2 is slightly n-type with an indirect band gap of ∼ 1.1 eV and a measured energy band alignment significantly different from recent DFT calculations. These results demonstrate the feasibility and significant potential of fabricating 2D material based heterostructures with tunable band alignments for a variety of nanoelectronic and optoelectronic applications.


[Structure-functional change in streptokinase exposed to ultrasound].
To optimize conditions of acousto-enzymatic thrombolysis the influence of low-frequency ultrasound on the isolated preparation of streptokinase was investigated. The ultrasound treatment with intensity 26 W/cm2 at 37 degrees C within 5-10 minutes was not accompanied by changes of structure-functional properties of the streptokinase molecule. Increase of ultrasound-processing time (10-60 minutes) resulted in non-covalent hydrophobic aggregation of some part of the protein. In contrast to native protein ultrasound modified streptokinase is readily degraded by plasmin with formation of polypeptide fragments with molecular weights ranged from 43 up to 14 kD. The processes of aggregation and increased proteolytic degradation resulted in lower efficiency of plasmin autoactivation under the action of sounded streptokinase.


[Roentgen diagnosis of the veins in the upper half of the body using the digital subtraction technic - digital subtraction phlebography].
Digital subtraction phlebography (DSP) is suitable for x-ray examinations of the shoulder veins and the veins of the upper mediastinum. Acute thromboses, post-thrombotic syndromes, malformations and collateral systems can be demonstrated. The main advantages of DSP over conventional phlebography are the possibility of using contrast medium solutions of low osmolarity enabling pain-free examinations not involving the risk of thromboses, the saving in the amount of contrast medium, and the reduction of examination time.


Somatic mutations, clinicopathologic characteristics, and survival in patients with untreated breast cancer with bone-only and non-bone sites of first metastasis.
Background: Bone is the most common site of metastasis of breast cancer. Biological mechanisms of metastasis to bone may be different from mechanisms of metastasis to non-bone sites, and identification of distinct signaling pathways and somatic mutations may provide insights on biology and rational targets for treatment and prevention of bone metastasis. The aims of this study were to compare and contrast somatic mutations, clinicopathologic characteristics, and survival in breast cancer patients with bone-only versus non-bone sites of first metastasis. Methods: Primary tumor samples were collected before treatment from 389 patients with untreated primary breast cancer and distant metastasis at diagnosis. In each sample, 46 or 50 cancer-related genes were analyzed for mutations by AmpliSeq Ion Torrent next-generation sequencing. Fisher's exact test was used to identify somatic mutations associated with bone-only first metastasis. Logistic regression models were used to identify differences in detected somatic mutations, clinicopathologic characteristics, and survival between patients with bone-only first metastasis and patients with first metastasis in non-bone sites only ("other-only first metastasis"). Results: Among the 389 patients, 72 (18.5%) had bone-only first metastasis, 223 (57.3%) had other-only first metastasis, and 94 (24.2%) had first metastasis in both bone and non-bone sites. The most commonly mutated genes were TP53 (N=103), PIK3CA (N=79), AKT (N=13), and PTEN (N=2). Compared to patients with other-only first metastasis, patients with bone-only first metastasis had higher rates of hormone-receptor-positive disease, non-triple-negative subtype, and lower grade (grade 1 or 2; Nottingham grading system) (all three comparisons, p<0.001); had a lower ratio of cases of invasive ductal carcinoma to cases of invasive lobular carcinoma (p=0.002); and tended to have a higher 5-year overall survival (OS) rate (78.2% [95% confidence interval (CI), 68.6%-89.0%] vs 55.0% [95% CI, 48.1%-62.9%]; p=0.051). However, in the subgroup of patients with TP53 mutation and in the subgroup of patients with PIK3CA mutation, OS did not differ between patients with bone-only and other-only first metastasis (p=0.49 and p=0.68, respectively). In univariate analysis, the rate of TP53 mutation tended to be lower in patients with bone-only first metastasis than in those with other-only first metastasis (15.3% vs 29.1%; p=0.051). In multivariate analysis, TP53 mutation was not significantly associated with site of first metastasis (p=0.54) but was significantly associated with hormone-receptor-negative disease (p<0.001). Conclusions: We did not find associations between somatic mutations and bone-only first metastasis in patients with untreated breast cancer. Patients with bone-only first metastasis tend to have longer OS than patients with other-only first metastasis. More comprehensive molecular analysis may be needed to further understand the factors associated with bone-only metastatic disease in breast cancer.


Falls from a balcony while intoxicated: a new injury trend among young adults?
Unintentional falls from heights, including balconies, result in life threatening traumatic injury. Alcohol, when combined with environmental factors and poor judgement, can potentially lead to fatal outcomes. One trauma center's registry identified a group of young adults falling from balconies and we investigated the role of alcohol. Hospital trauma service admissions from 2010 through 2017 were reviewed for unintentional falls from heights. Suicide attempts and unintentional falls off ladders or roofs were excluded. Data were obtained from trauma registry and medical record review, as well as social work service interviews. Falls from heights comprised 4.8% of injuries treated at our trauma center during the eight-year study period with 98.5% admitted. Of patients admitted because of falls, 10.3% (55/532) were from a balcony. The majority of this group of patients was male and 19-29 years old (67%). Of patients with a blood alcohol concentration (BAC) determination, 62% had a positive BAC upon hospital admission with an average of 0.20 g/dL among those 34 patients. No gender differences were evident for alcohol use. Seven of the eight patients under the legal drinking age of 21 years were a subgroup with high alcohol use as compared with patients 21 years and older (p = 0.099). Ninety-four percent of falls occurred at residential locations such as dormitories or apartment complexes, often during a social event. Backward falls off railings and attempts to jump to adjoining balconies were common. Head, thorax/abdomen, and extremity fractures were common, with an average injury severity score (ISS) of 16. Average length of hospital stay was 8 days. Most patients (67%) were discharged home after hospital stay, but 21% were transferred to inpatient rehabilitation or skilled nursing facilities. There were two deaths. Falls from balconies among young adults occur in our area yet the true frequency of these events remain unknown. Occurrence was most common among underage drinkers. Generalization is difficult with this small sample, yet high risk behaviors and environmental factors were evident. It is imperative that educational programs focus on this population with collaborative prevention efforts focused on the dangers of, and increased risk of injury associated with the balcony environment.


Surgical treatment of mass-forming intrahepatic cholangiocarcinoma: an 11-year Western single-center experience in 107 patients.
Hepatic resection is the only cure for intrahepatic cholangiocellular carcinoma (ICC). The purpose of this study was to clarify the clinicopathologic characteristics and surgical outcome of patients with ICC. We retrospectively studied the records of 67 patients who underwent laparotomy for ICC from January 1995 through December 2005. Univariate and multivariate analyses were conducted for several variables to evaluate their influence on the outcome. Forty-five patients underwent hepatic resection. In 19 patients, the tumors were found to be unresectable at the time of laparotomy. Median 2- and 5-year survival rates in the 45 resected patients were 62% and 35%, respectively. For 36 patients who underwent curative resection, the 2- and 5-year survival were 67% and 41%, respectively; with a median survival of 43 months. The overall 5-year recurrence-free survival was 30%. The 90-day postoperative mortality rate was 4% and morbidity 28%. Multivariate analyses confirmed resection margin, lymph node involvement, blood loss, and blood transfusion to be independent significant variables for overall survival. Predictors of longer recurrence-free survival were lymph node involvement, vascular infiltration, blood loss, and transfusion. Surgical treatment of ICC by curative hepatic resection in patients without nodal invasion provides good long-term results. In contrast, incomplete tumor removal does not provide a survival benefit. An improved quality of preoperative staging was able to increase the resectability rate to acceptable 70%.


Emotional and behavioural difficulties in children with diabetes: a controlled comparison with siblings and peers.
This study describes a comparison of children with insulin dependent diabetes mellitus (IDDM) with two control groups: the sibling nearest to them in age, and peers matched for gender and age. A broad range of emotional and behavioural difficulties were assessed using the Conners' Teachers' and Parents' rating scales (CTRS 39 and CPRS 93). Individually completed children's questionnaires provided qualitative data about the children's problems. The results of the study showed markedly higher scores for the children with diabetes on the parent scales on factors such as hyperactivity, psychosomatic and restless/disorganized, in comparison to their siblings, but not their peers. These differences were not found on the Teachers' Scales. The findings are discussed in terms of parental perceptions of children with diabetes and the difficulties these children and their siblings experience in their lives. Suggestions are made for further research.


Silver-Russell syndrome and exclusion of uniparental disomy.
Recently, maternal uniparental disomy for the entire chromosome 7 was described in three of 25 Silver-Russell syndrome sporadic cases, yet the etiology of the remaining cases is unclear. Two cases with Silver-Russell syndrome and a balanced translocation involving the 17q25 had been reported. We looked for evidence of genomic imprinting due to uniparental disomy 17 in seven patients with sporadic Silver-Russell syndrome and their parents. Additionally, chromosomes 7, 8, 11 and 20 were studied. Uniparental disomy was ruled out for all these chromosomes in six of seven families; one family was informative only for chromosome 17. Not-withstanding our negative results, it is still possible that uniparental disomy plays a part in this syndrome. A mutation in a Mendelian gene in 17q25 could also account for the Silver-Russell syndrome etiology.


Molecular characterization of dihydroneopterin aldolase and aminodeoxychorismate synthase in common bean-genes coding for enzymes in the folate synthesis pathway.
Common beans (Phaseolus vulgaris) are excellent sources of dietary folates, but different varieties contain different amounts of these compounds. Genes coding for dihydroneopterin aldolase (DHNA) and aminodeoxychorismate synthase (ADCS) of the folate synthesis pathway were characterized by PCR amplification, BAC clone sequencing, and whole genome sequencing. All DHNA and ADCS genes in the Mesoamerican cultivar OAC Rex were isolated and compared with those genes in the genome of Andean genotype G19833. Both genotypes have two functional DHNA genes and one pseudo gene. PvDHNA1 and PvDHNA2 proteins have similar secondary structures and conserved residues as DHNA homologs in Staphylococcus aureus and Arabidopsis. Sequence analysis and synteny mapping indicated that PvDHNA1 might be a duplicated and transposed copy of PvDHNA2. There is only one ADCS gene (PvADCS) identified in the bean genome and it is identical in OAC Rex and G19833. PvADCS has the conserved motifs required for catalytic activity similar to other plant ADCS homologs. DHNA and ADCS gene-specific markers were developed, mapped, and compared to their physical locations on chromosomes 1 and 7, respectively. The gene-specific markers developed in this study should be useful for detection and selection of varieties with enhanced folate contents in bean breeding programs.


Virgin coconut oil complements with its polyphenol components mitigate sodium fluoride toxicity in vitro and in vivo.
Virgin coconut oil (VCO), prepared from fresh coconut kernel without any chemical refining, is an emerging functional food. The pharmacological benefits of VCO are believed to be due to the natural combination of phenolics. Although cell culture studies have demonstrated the antioxidant activity of VCO under different oxidative stress conditions, a valid in vivo demonstration of the antioxidant activity of VCO is yet to come. Sodium fluoride (NaF), an environmental pollutant, is widely used to induce oxidative stress in cell culture models and rodents to test the antioxidant potential of several compounds. Herein, VCO and its polyphenolic (VCOP) and non-phenolic oil fraction (VCOF) were individually tested in fluoride-exposed normal intestinal cells (IEC-6) and mice to address their contribution to the documented antioxidant potential. It was found that pretreatment of VCOP (40 µg/mL) was effective in mitigating the fluoride-induced cell death when compared to VCO (200 µg/mL) and VCOF (160 µg/mL). Further, exposure to fluoride (10 mM), increased the intracellular ROS measured based on the dichlorofluorescein (DCF) fluorescence, and this, in turn, was significantly reduced when the cells were supplemented with VCOP. Oral administration of VCO (2 mL/kg bwt) reversed the drop in the hepatic catalase and SOD activities to near normal with a minimal level of lipid peroxidation in fluoride intoxicated mice. However, VCOP and VCOF were less effective in lowering the fluoride-induced increase in hepatic oxidative stress markers. It is reasoned that the oil components of VCO complement the natural antioxidant molecules resulting in an overall increase in their bioavailability.


Benefits of a Pediatric Clinic Simulation Using Standardized Patients in Family Nurse Practitioner Education.
The purpose of this study was to examine the effect of a pediatric clinic simulation with standardized patients on anxiety, self-efficacy, and performance in family nurse practitioner students. A pediatric clinic simulation was developed in which family nurse practitioner students encountered standardized patients presenting for a well-child visit or exhibiting a common chief complaint. Anxiety and self-efficacy were assessed pre/post the simulation intervention, along with faculty-observed student performance. The clinic simulation resulted in increased self-efficacy, lower anxiety, and improved performance (p < .01). High-fidelity simulation of a pediatric clinic was found to foster development of clinical competency, lower student anxiety, and improve self-efficacy.


Different Sources of Stem Cells and their Application in Cartilage Tissue Engineering.
The articular cartilage is unique in that it contains only a single type of cell and shows poor ability for spontaneous healing. Currently, approaches for treating cartilage defects include surgical and nonsurgical approaches, as well as cartilage tissue engineering. For standard cartilage tissue engineering, three elements are required, i.e., a scaffold, growth factors, and seed cells. With advancements in stem cell research, the main sources of cells for cartilage tissue engineering are embryonic and mesenchymal stem cells, which have been shown to be promising alternatives in recent years. In this review, we focus on the applications of various stem cells in cartilage tissue engineering. Under certain conditions, several types of stem cells, including embryonic stem cells, mesenchymal stem cells, induced pluripotent stem cells, and cartilage progenitor cells, showed potential for applications in chondrogenic differentiation. Stem cells can be developed as important cell sources for cartilage tissue engineering if appropriate microenvironments and bioactive factors are supplied. However, further studies are needed to determine the ideal cell type for cartilage repair, particularly using in vivo and clinical studies.


Temporal frequency and chromatic processing in humans: an fMRI study of the cortical visual areas.
Psychophysical sensitivity to isoluminant chromatic modulation declines at temporal frequencies beyond 4 Hz, whereas chromatically opponent cells of the afferent visual pathway (long- to middle-wavelength (L-M) cone-opponent or short-wavelength (S) cone cells) show responses at much higher temporal frequencies, indicating a central limitation in temporal processing capacity. Here, we sought to localize this limit in cortical retinotopic visual areas. We used fMRI to investigate responses of lateral geniculate nucleus and cortical visual areas in humans to isoluminant chromatic modulation as a function of temporal frequency (2-12 Hz). Our results suggest that L-M cone-opponent and S-cone signals are processed in LGN up to 12 Hz. In all visual areas except MT (middle temporal) and V3a, S-cone responses declined steeply with temporal frequency, implying that psychophysical sensitivity loss to blue-yellow modulation might occur early within these areas. While V1 showed robust L-M responses up to 12 Hz, there was a progressive falloff of responses with temporal frequency as information is transferred from V1 to higher areas (V2, V3, and V4), suggesting that, in humans, temporal limitation in perception of red-green chromatic modulation likely results from limited processing capacity of higher ventral extrastriate areas.


Communication Among Melanoma Family Members.
Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the Case) and an additional first degree relative and a parent of a child 0-17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at 1 year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range = 14-18 percentage points; all p < .05). At baseline, approximately two-thirds of all three family members talked with at least some member of the family about cancer risk. Agreement between Cases and First Degree Relatives and between Cases and Parents increased from pre to post intervention in the intervention participants compared to the control participants (p < .05). These findings provide support for interventions to improve family communication about cancer risk.


Normal levels of constitutive and death receptor-mediated apoptosis of peripheral blood neutrophils from patients with chronic idiopathic neutropenia.
To investigate the role of neutrophil apoptosis in the pathogenesis of chronic neutropenia, we examined constitutive and death receptor-mediated apoptosis ex vivo of peripheral blood neutrophils obtained from six chronic idiopathic neutropenia (CIN) patients and six healthy adult blood donors. Apoptosis was quantified based on phosphatidylserine externalization and caspase-3 activation in freshly isolated neutrophils or after overnight cultivation of neutrophils in the absence or presence of pro- or anti-apoptotic factors, including the pan-caspase inhibitor, zVAD-fmk. Neutrophils from CIN patients receiving treatment with granulocyte colony-stimulating factor appeared to be more prone to constitutive apoptosis than cells from untreated patients; however, further investigations in larger cohorts of patients are needed to validate these pilot studies. Overall, the level of neutrophil apoptosis was similar in patient and control groups, thus supporting the notion that the underlying defect in these neutropenia patients lies elsewhere, such as in the bone marrow microenvironment.


Six ways to maximize survey response rates: lessons from a medical school accreditation survey in a Canadian setting.
Surveys are being increasingly used to gather feedback and study data in healthcare professions. However, it may be challenging to achieve high response rates in surveys administered to healthcare professionals. The aim of this paper is to report six strategies that contributed to a high response rate on the Independent Student Analysis at the University of Toronto (U of T), which can be applied to other surveys to achieve strong response rates amongst healthcare professionals. In 2019, as part of accreditation for the U of T MD Program, we conducted the Independent Student Analysis, a student-led survey examining a medical student's experience. We review and critically evaluate the factors that contributed to a robust response rate amongst one of the largest cohorts of medical students in Canada. Among 1080 students in the MD program, we achieved an unprecedented response rate of 87.2%. Six factors were identified that most contributed to our high response rate, including: faculty support, student representation, eliciting participant feedback, creating protected time for completion, offering incentives, and generating awareness. Eliciting high survey response rates from medical learners can be challenging. However, with careful consideration of learner feedback and effective employment of the strategies discussed in this paper, medical school faculty may better engage students in survey completion, achieving higher response rates and gathering richer insight, which can be used to more effectively enact meaningful change amongst healthcare professionals.